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JAMA Internal Medicine Apr 2024The effect of testosterone replacement therapy (TRT) in men with hypogonadism on the risk of progression from prediabetes to diabetes or of inducing glycemic remission...
IMPORTANCE
The effect of testosterone replacement therapy (TRT) in men with hypogonadism on the risk of progression from prediabetes to diabetes or of inducing glycemic remission in those with diabetes is unknown.
OBJECTIVE
To evaluate the efficacy of TRT in preventing progression from prediabetes to diabetes in men with hypogonadism who had prediabetes and in inducing glycemic remission in those with diabetes.
DESIGN, SETTING, AND PARTICIPANTS
This nested substudy, an intention-to-treat analysis, within a placebo-controlled randomized clinical trial (Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men [TRAVERSE]) was conducted at 316 trial sites in the US. Participants included men aged 45 to 80 years with hypogonadism and prediabetes or diabetes who were enrolled in TRAVERSE between May 23, 2018, and February 1, 2022.
INTERVENTION
Participants were randomized 1:1 to receive 1.62% testosterone gel or placebo gel until study completion.
MAIN OUTCOMES AND MEASURES
The primary end point was the risk of progression from prediabetes to diabetes, analyzed using repeated-measures log-binomial regression. The secondary end point was the risk of glycemic remission (hemoglobin A1c level <6.5% [to convert to proportion of total hemoglobin, multiply by 0.01] or 2 fasting glucose measurements <126 mg/dL [to convert to mmol/L, multiply by 0.0555] without diabetes medication) in men who had diabetes.
RESULTS
Of 5204 randomized participants, 1175 with prediabetes (mean [SD] age, 63.8 [8.1] years) and 3880 with diabetes (mean [SD] age, 63.2 [7.8] years) were included in this study. Mean (SD) hemoglobin A1c level in men with prediabetes was 5.8% (0.4%). Risk of progression to diabetes did not differ significantly between testosterone and placebo groups: 4 of 598 (0.7%) vs 8 of 562 (1.4%) at 6 months, 45 of 575 (7.8%) vs 57 of 533 (10.7%) at 12 months, 50 of 494 (10.1%) vs 67 of 460 (14.6%) at 24 months, 46 of 359 (12.8%) vs 52 of 330 (15.8%) at 36 months, and 22 of 164 (13.4%) vs 19 of 121 (15.7%) at 48 months (omnibus test P = .49). The proportions of participants with diabetes who experienced glycemic remission and the changes in glucose and hemoglobin A1c levels were similar in testosterone- and placebo-treated men with prediabetes or diabetes.
CONCLUSIONS AND RELEVANCE
In men with hypogonadism and prediabetes, the incidence of progression from prediabetes to diabetes did not differ significantly between testosterone- and placebo-treated men. Testosterone replacement therapy did not improve glycemic control in men with hypogonadism and prediabetes or diabetes. These findings suggest that TRT alone should not be used as a therapeutic intervention to prevent or treat diabetes in men with hypogonadism.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03518034.
Topics: Male; Humans; Middle Aged; Testosterone; Prediabetic State; Glycated Hemoglobin; Hypogonadism; Hormone Replacement Therapy; Glucose
PubMed: 38315466
DOI: 10.1001/jamainternmed.2023.7862 -
High Blood Pressure & Cardiovascular... Nov 2023The worldwide impressive growth of metabolic disorders observed in the last decades, especially type 2 diabetes mellitus and obesity, has generated great interest in the... (Review)
Review
The worldwide impressive growth of metabolic disorders observed in the last decades, especially type 2 diabetes mellitus and obesity, has generated great interest in the potential benefits of early identification and management of patients at risk. In this view, prediabetes represents a high-risk condition for the development of type 2 diabetes mellitus and cardiovascular diseases, and an ideal target to intercept patients before they develop type 2 diabetes gaining a prominent role even in international guidelines. For prediabetic individuals, lifestyle modification is the cornerstone of diabetes prevention, with evidence of about 50% relative risk reduction. Accumulating data also show potential benefits from pharmacotherapy. In this context, the only available data pertain to metformin as a pharmaceutical drug and vitamin D and L-arginine as nutraceuticals. L-arginine appears to be a very interesting tool in the clinical management of patients with pre-diabetes. In this review we summarize the current knowledge on the role of L-arginine in prediabetes as a potentially useful preventive strategy against the progression to type 2 diabetes, with a particular focus on the underlying molecular mechanisms and the past and ongoing trials. In this article we also report the interesting data about the perception of the prediabetic condition and its therapeutic management in the clinical practice in Italy. An early identification and a prompt management of people with prediabetes appears to be of paramount importance to prevent the progression to diabetes and avoid its cardiovascular consequences.
Topics: Humans; Prediabetic State; Diabetes Mellitus, Type 2; Metformin; Vitamins; Arginine
PubMed: 38060094
DOI: 10.1007/s40292-023-00613-1 -
BMC Medicine Dec 2023Whether a low-inflammatory diet relates to type 2 diabetes risk remains unclear. We examined the association between a low-inflammatory diet and risk of type 2 diabetes...
BACKGROUND
Whether a low-inflammatory diet relates to type 2 diabetes risk remains unclear. We examined the association between a low-inflammatory diet and risk of type 2 diabetes among normoglycemic and prediabetic participants. We also explored whether a low-inflammatory diet modifies genetic risk for type 2 diabetes.
METHODS
Among 142,271 diabetes-free UK Biobank participants (aged 39-72 years), 126,203 were normoglycemic and 16,068 were prediabetic at baseline. Participants were followed for up to 15 years to detect incident type 2 diabetes. At baseline, dietary intake was assessed with a 24-h dietary record. An inflammatory diet index (IDI) was generated based on high-sensitivity C-reactive protein levels and was a weighted sum of 34 food groups (16 anti-inflammatory and 18 pro-inflammatory). Participants were grouped into tertiles corresponding to inflammatory level (low, moderate, and high) based on IDI scores. Prediabetes at baseline was defined as HbA1c 5.7-6.4% in diabetes-free participants. Incident type 2 diabetes and age of onset were ascertained according to the earliest recorded date of type 2 diabetes in the Primary Care and Hospital inpatient data. A diabetes-related genetic risk score (GRS) was calculated using 424 single-nucleotide polymorphisms. Data were analyzed using Cox regression and Laplace regression.
RESULTS
During follow-up (median 8.40 years, interquartile range 6.89 to 11.02 years), 3348 (2.4%) participants in the normoglycemia group and 2496 (15.5%) in the prediabetes group developed type 2 diabetes. Type 2 diabetes risk was lower in normoglycemic (hazard ratio [HR] = 0.71, 95% confidence interval [CI] 0.65, 0.78) and prediabetic (HR = 0.81, 95% CI 0.73, 0.89) participants with low IDI scores compared to those with high IDI scores. A low-inflammatory diet may prolong type 2 diabetes onset by 2.20 (95% CI 1.67, 2.72) years among participants with normoglycemia and 1.11 (95% CI 0.59, 1.63) years among participants with prediabetes. In joint effect analyses, normoglycemic or prediabetes participants with low genetic predisposition to type 2 diabetes and low IDI scores had a significant 74% (HR = 0.26, 95% CI 0.21, 0.32) or 51% (HR = 0.49, 95% CI 0.40, 0.59) reduction in type 2 diabetes risk compared to those with high genetic risk plus high IDI scores. There were significant additive and multiplicative interactions between IDI and GRS in relation to type 2 diabetes risk in the normoglycemia group.
CONCLUSIONS
A low-inflammatory diet is associated with a decreased risk of type 2 diabetes and may delay type 2 diabetes onset among participants with normal blood glucose or prediabetes. A low-inflammatory diet might significantly mitigate the risk of genetic factors on type 2 diabetes development.
Topics: Humans; Prediabetic State; Diabetes Mellitus, Type 2; Incidence; Blood Glucose; Risk Factors; Diet
PubMed: 38049803
DOI: 10.1186/s12916-023-03190-1 -
Environment International Nov 2023The cardiometabolic health status of Inuit in Nunavik has worsened in the last thirty years. The high concentrations of perfluoroalkyl acids (PFAAs) may be contributing...
INTRODUCTION
The cardiometabolic health status of Inuit in Nunavik has worsened in the last thirty years. The high concentrations of perfluoroalkyl acids (PFAAs) may be contributing to this since PFAAs have been linked with hypercholesterolemia, diabetes, and high blood pressure. The aim of this study was to examine the association between a PFAAs mixture and lipid profiles, Type II diabetes, prediabetes, and high blood pressure in this Inuit population.
METHODS
We included 1212 participants of the Qanuilirpitaa? 2017 survey aged 16-80 years. Two mixture models (quantile g-computation and Bayesian Kernel Machine Regression (BKMR)) were used to investigate the associations between six PFAAs (PFHxS, PFOS, PFOA and three long-chain PFAAs (PFNA, PFDA and PFUnDA)) with five lipid profiles and three cardiometabolic outcomes. Non-linearity and interaction between PFAAs were further assessed.
RESULTS
An IQR increase in all PFAAs congeners resulted in an increase in total cholesterol (β 0.15, 95% confidence interval (CI) 0.06, 0.24), low-density lipoprotein cholesterol (LDL) (β 0.08, 95% CI 0.01, 0.16), high-density lipoprotein cholesterol (HDL) (β 0.04, 95% CI 0.002, 0.08), apolipoprotein B-100 (β 0.03, 95% CI 0.004, 0.05), and prediabetes (OR 1.80, 95% CI 1.11, 2.91). There was no association between PFAAs and triglycerides, diabetes, or high blood pressure. Long-chain PFAAs congeners were the main contributors driving the associations. Associations were largely linear, and there was no evidence of interaction between the PFAAs congeners.
CONCLUSIONS
Our study provides further evidence of increasing circulating lipids with increased exposure to PFAAs. The increased risk of prediabetes points to the influence of PFAAs on potential clinical outcomes. International regulation of PFAAs is essential to curb PFAAs exposure and related health effects in Arctic communities.
Topics: Humans; Diabetes Mellitus, Type 2; Prediabetic State; Bayes Theorem; Inuit; Fluorocarbons; Cholesterol; Hypertension; Cardiovascular Diseases; Alkanesulfonic Acids; Environmental Pollutants
PubMed: 37883911
DOI: 10.1016/j.envint.2023.108283 -
Journal of the National Comprehensive... Nov 2023Individuals with diabetes and prediabetes are at increased risk of pancreatic cancer. However, little is known about the effects of smoking or smoking cessation on...
BACKGROUND
Individuals with diabetes and prediabetes are at increased risk of pancreatic cancer. However, little is known about the effects of smoking or smoking cessation on pancreatic cancer risk in individuals with diabetes and prediabetes. We investigated the association between smoking status (particularly smoking cessation) and pancreatic cancer risk according to glycemic status.
PATIENTS AND METHODS
This nationwide cohort study included 9,520,629 adults without cancer who underwent the Korean National Health Screening in 2009 and were followed until 2018. Hazard ratios and 95% confidence intervals for pancreatic cancer were estimated after adjusting for potential confounders.
RESULTS
During the 78.4 million person-years of follow-up, 15,245 patients were newly diagnosed with pancreatic cancer. Among individuals with diabetes and prediabetes, current smoking synergistically increased pancreatic cancer risk (all P<.01). However, quitters with diabetes and prediabetes had a pancreatic cancer risk comparable to that of never-smokers (all P>.05). For pancreatic cancer in current smokers, quitters, and never-smokers, respectively, the hazard ratios were 1.48 (95% CI, 1.40-1.58), 1.11 (95% CI, 1.03-1.19), and 1.00 (reference) among individuals with normoglycemia; 1.83 (95% CI, 1.70-1.97), 1.28 (95% CI, 1.18-1.39), and 1.20 (95% CI, 1.14-1.26) among individuals with prediabetes; and 2.72 (95% CI, 2.52-2.94), 1.78 (95% CI, 1.63-1.95), and 1.63 (95% CI, 1.54-1.72) among individuals with diabetes. There were no differences in risk between quitters with a <20 pack-year smoking history and never-smokers in all glycemic status groups.
CONCLUSIONS
Pancreatic cancer risk synergistically increased in current smokers with diabetes and prediabetes. However, smoking cessation reduced the synergistically increased risk of pancreatic cancer to the level of never-smokers, especially when smoking history was <20 pack-years. More individualized and intensive cancer prevention education should be underscored for individuals at an increased risk of pancreatic cancer beyond the one-size-fits-all approach.
Topics: Adult; Humans; Smoking Cessation; Smoking; Cohort Studies; Prediabetic State; Pancreatic Neoplasms; Risk Factors
PubMed: 37935099
DOI: 10.6004/jnccn.2023.7060 -
Diabetes/metabolism Research and Reviews May 2024Metabolic dysfunction-associated fatty liver disease (MAFLD, 2020 diagnostic criteria) and glomerular hyperfiltration share common risk factors, including obesity,...
BACKGROUND
Metabolic dysfunction-associated fatty liver disease (MAFLD, 2020 diagnostic criteria) and glomerular hyperfiltration share common risk factors, including obesity, insulin resistance, impaired glucose tolerance, diabetes, dyslipidemia, and hypertension.
AIMS
To assess the prevalence of MAFLD and its association with glomerular hyperfiltration and age-related worsening of kidney function in subjects with normoglycemia, prediabetes and type 2 diabetes mellitus (T2DM).
METHODS
We analysed data recorded during occupational health visits of 125,070 Spanish civil servants aged 18-65 years with a de-indexed glomerular filtration rate (GFR) estimated with the chronic-kidney-disease-epidemiological (CKD-EPI) equation (estimated glomerular filtration rate [eGFR]) ≥60 mL/min. Subjects were categorised according to fasting plasma glucose levels <100 mg/dL (normoglycemia), ≥100 and ≤ 125 mg/dL (prediabetes), or ≥126 mg/dL and/or antidiabetic treatment (T2DM). The association between MAFLD and glomerular hyperfiltration, defined as a de-indexed eGFR above the age- and gender-specific 95th percentile, was assessed by multivariable logistic regression.
RESULTS
In the whole study group, MAFLD prevalence averaged 19.3%. The prevalence progressively increased from 14.7% to 33.2% and to 48.9% in subjects with normoglycemia, prediabetes and T2DM, respectively (p < 0.001 for trend). Adjusted odds ratio (95% CI) for the association between MAFLD and hyperfiltration was 9.06 (8.53-9.62) in the study group considered as a whole, and 8.60 (8.03-9.21), 9.52 (8.11-11.18) and 8.31 (6.70-10.30) in subjects with normoglycemia, prediabetes and T2DM considered separately. In stratified analyses, MAFLD amplified age-dependent eGFR decline in all groups (p < 0.001).
CONCLUSIONS
MAFLD prevalence increases across the glycaemic spectrum. MAFLD is significantly associated with hyperfiltration and amplifies the age-related eGFR decline.
Topics: Humans; Diabetes Mellitus, Type 2; Prediabetic State; Male; Female; Middle Aged; Cross-Sectional Studies; Adult; Glomerular Filtration Rate; Aged; Young Adult; Adolescent; Blood Glucose; Risk Factors; Prevalence; Non-alcoholic Fatty Liver Disease; Prognosis; Follow-Up Studies; Biomarkers; Diabetic Nephropathies
PubMed: 38757431
DOI: 10.1002/dmrr.3810 -
Cardiovascular Diabetology Sep 2023Patients with type 2 diabetes have an increased risk of death and cardiovascular events and people with diabetes or prediabetes have been found to have increased...
BACKGROUND
Patients with type 2 diabetes have an increased risk of death and cardiovascular events and people with diabetes or prediabetes have been found to have increased atherosclerotic burden in the coronary and carotid arteries. This study will estimate the cross-sectional prevalence of atherosclerosis in the coronary and carotid arteries in individuals with prediabetes and diabetes, compared with normoglycaemic individuals in a large population-based cohort.
METHODS
The 30,154 study participants, 50-64 years, were categorized according to their fasting glycaemic status or self-reported data as normoglycaemic, prediabetes, and previously undetected or known diabetes. Prevalence of affected coronary artery segments, severity of stenosis and coronary artery calcium score (CACS) were determined by coronary computed tomography angiography. Total atherosclerotic burden was assessed in the 11 clinically most relevant segments using the Segment Involvement Score and as the presence of any coronary atherosclerosis. The presence of atherosclerotic plaque in the carotid arteries was determined by ultrasound examination.
RESULTS
Study participants with prediabetes (n = 4804, 16.0%) or diabetes (n = 2282, 7.6%) had greater coronary artery plaque burden, more coronary stenosis and higher CACS than normoglycaemic participants (all, p < 0.01). Among male participants with diabetes 35.3% had CACS ≥ 100 compared to 16.1% among normoglycaemic participants. For women, the corresponding figures were 8.9% vs 6.1%. The prevalence of atherosclerosis in the coronary arteries was higher in participants with previously undetected diabetes than prediabetes, but lower than in patients with known diabetes. The prevalence of any plaque in the carotid arteries was higher in participants with prediabetes or diabetes than in normoglycaemic participants.
CONCLUSIONS
In this large population-based cohort of currently asymptomatic people, the atherosclerotic burden in the coronary and carotid arteries increased with increasing degree of dysglycaemia. The finding that the atherosclerotic burden in the coronary arteries in the undetected diabetes category was midway between the prediabetes category and patients with known diabetes may have implications for screening strategies and tailored prevention interventions for people with dysglycaemia in the future.
Topics: Humans; Female; Male; Prediabetic State; Diabetes Mellitus, Type 2; Cross-Sectional Studies; Prevalence; Sweden; Atherosclerosis; Plaque, Atherosclerotic
PubMed: 37759237
DOI: 10.1186/s12933-023-01982-6 -
Primary Care Diabetes Aug 2023
Topics: Humans; Prediabetic State; Diabetes Mellitus, Type 2
PubMed: 37394313
DOI: 10.1016/j.pcd.2023.06.010 -
Association between dietary inflammatory index and low muscle mass in diabetes/prediabetes patients.Experimental Gerontology Aug 2023Growing evidence has increasingly validated that individuals with diabetes/prediabetes have a higher prevalence of low skeletal muscle mass and function compared to...
BACKGROUND
Growing evidence has increasingly validated that individuals with diabetes/prediabetes have a higher prevalence of low skeletal muscle mass and function compared to healthy individuals. The anti-inflammatory diet is considered a promising and modifiable approach to optimize skeletal muscle quality. However, current evidence on the relation of dietary inflammatory potential with low muscle mass among diabetic/prediabetic patients is limited.
METHODS
Dietary consumption was determined by trained staff using the 24-hour diet recall method, and the Dietary Inflammatory Index (DII) was scored based on a previously validated approach that included 26 food parameters. Dual-energy X-ray absorptiometry was used to assess the mass of skeletal muscle and low muscle mass was defined based on the sarcopenia index. Logistic regression was conducted to calculate odds ratios (ORs) and 95 % confidence intervals (CIs). Restricted cubic spline (RCS) analysis was also performed to visually represent the relationship between DII and low muscle mass. Furthermore, sensitivity and subgroup analyses were conducted.
RESULTS
In this study, a total of 4269 eligible participants were registered, comprising 1975 (46.26 %) females and 2294 (53.74 %) males. The mean age was 49.98 ± 0.31 years old, and the mean DII score was 1.53 ± 0.04. Among them, 934 (21.88 %) patients were defined as having low muscle mass, while 3335 (78.12 %) were without low muscle mass. The highest tertile (T3) of DII had an 61 % increased risk of low muscle mass (OR = 1.61, 95%CI: 1.19-2.17, p for trend = 0.004) compared to the lowest tertile. The RCS curve displayed a linear dose-response relationship between DII score and low muscle mass risk in patients with diabetes/prediabetes. Subgroup and sensitivity analyses provided robustness to our results.
CONCLUSIONS
Our results indicated that a higher DII score was associated with an increased risk of low muscle mass among diabetes/prediabetes patients. These findings provided a nutritional strategy for diabetes/prediabetes patients to prevent skeletal muscle mass loss.
Topics: Humans; Diet; Diabetes Mellitus; Prediabetic State; Muscle, Skeletal; Inflammation; Nutrition Surveys; Male; Female; Adult; Middle Aged
PubMed: 37460025
DOI: 10.1016/j.exger.2023.112258 -
Journal of Neurochemistry Jul 2023Schwann cells (SCs) support peripheral nerves under homeostatic conditions, independent of myelination, and contribute to damage in prediabetic peripheral neuropathy...
Schwann cells (SCs) support peripheral nerves under homeostatic conditions, independent of myelination, and contribute to damage in prediabetic peripheral neuropathy (PN). Here, we used single-cell RNA sequencing to characterize the transcriptional profiles and intercellular communication of SCs in the nerve microenvironment using the high-fat diet-fed mouse, which mimics human prediabetes and neuropathy. We identified four major SC clusters, myelinating, nonmyelinating, immature, and repair in healthy and neuropathic nerves, in addition to a distinct cluster of nerve macrophages. Myelinating SCs acquired a unique transcriptional profile, beyond myelination, in response to metabolic stress. Mapping SC intercellular communication identified a shift in communication, centered on immune response and trophic support pathways, which primarily impacted nonmyelinating SCs. Validation analyses revealed that neuropathic SCs become pro-inflammatory and insulin resistant under prediabetic conditions. Overall, our study offers a unique resource for interrogating SC function, communication, and signaling in nerve pathophysiology to help inform SC-specific therapies.
Topics: Mice; Humans; Animals; Myelin Sheath; Prediabetic State; Single-Cell Gene Expression Analysis; Schwann Cells; Peripheral Nerves; Peripheral Nervous System Diseases
PubMed: 37328915
DOI: 10.1111/jnc.15877